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Biomedical subjects

J D Pirsch

Publications and source records attributed to J D Pirsch.

At least 163 records · Page 9Linked to original sources

Early diagnosis and treatment of pancreas allograft rejection.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Living-unrelated renal transplantation: results in 40 patients.

Kidney transplantation for the treatment of end-stage renal disease has been limited by an inadequate number of donor organs. Because of the enormous impact kidney transplantation can have for patients, the authors have performed 40 living-unrelated donor renal transplantations using a donor-specific transfusion protocol since 1981. Ten additional patients were entered but became sensitized. Donors included 23 wives, seven husbands, six friends, and four individuals related by marriage. Type I diabetes was the most common indication for transplantation (45%). Despite 36 rejections in 24 patients (27 of 36 [75%] in the early postoperative period), only two grafts failed because of rejection. Twenty-one of these rejections responded to high-dose prednisone alone; the remainder required antilymphocyte globulin therapy or plasmapheresis. Sixteen patients had no acute rejections. Three other grafts were lost, including two deaths: one myocardial infarction (with a functioning graft), and one death secondary to a postoperative cecal perforation. One graft was lost from infarction after percutaneous nephrostomy placement. Of 40 grafts, 34 were functioning with a mean serum creatinine of 1.7 mg/dL (at a mean follow-up time of 27 months). Actuarial patient and graft survival were 94% and 89%, respectively, at 3 years. Living-unrelated renal transplants are an acceptable alternative to cadaver transplants, with excellent graft and patient survival.

Adult↗

Experience with simultaneous pancreas-kidney transplantation.

With refinements in surgical techniques and increased clinical experience, there has been a resurgence of interest in vascularized pancreas transplantation. From December 1986 to April 1988, 30 whole-organ vascularized pancreas transplants with pancreatico duodenocystostomy were performed simultaneously with renal transplantation. The recipient population consisted of 20 men and ten women, with a mean age of 34.7 years (range of 25-53 years). The mean duration of insulin-dependent diabetes mellitus (IDDM) was 22.6 years (range of 10-37 years). The mean pancreas preservation time was 8.7 hours (range 3-19 years). All patients were immediately insulin-independent. Simultaneous pancreas-kidney engraftment was performed to both iliac fossae via a lower midline incision (n = 28) or through a bilateral lower abdominal incision (n = 2). The mean operating time was 5.9 hours, and packed cell transfusion requirement was 1.3 units. The mean length of hospital stay was 27.4 days. Recipients averaged 2.3 admissions (1-7), with ten patients (34.4%) requiring only one hospital admission. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and Minnesota antilymphoblast globulin (MALG). A total of 49 episodes of rejection occurred in 26 patients. Actuarial patient survival rate at two years is 96.3%. The kidney and pancreas survival rates for the same time interval is 94.0% and 84.0%, respectively. Mean serum creatinine at present is 1.75 mg/dl. In conclusion, renal transplantation in concert with pancreas transplantation has a dramatic positive impact on pancreas allograft survival. Combined engraftment does not appear to jeopardize renal allograft functional survival. In view of these results, simultaneous pancreas-kidney transplantation appears to be the treatment of choice for Type I diabetic patients.

Adult↗

Withdrawal of steroid immunosuppression in renal transplant recipients.

The complications of long-term steroid immunosuppression are well known. During a 12-month period, 52 living-donor renal transplant recipients were entered into a protocol of intentional early steroid withdrawal. Selection criteria were primary living-related renal transplants in HLA-identical (12) or one-haplotype match (40) patients. The study population consisted of 25 diabetics (48.1%) with a mean age of 32.4 years. All patients received preoperative blood transfusions (3 donor-specific in haplotype-matched, 3 random in HLA-identical recipients). Immunosuppression consisted of cyclosporine, azathioprine, and corticosteroids, with deliberate steroid withdrawal after two weeks. Forty-six patients (88.5%) were successfully tapered off steroids, while the six protocol failures (11.5%) were due to early rejection or leukopenia that prevented steroid withdrawal. Twenty-three patients (50%) subsequently were returned to steroid therapy for rejection (21) or leukopenia (2). Inadequate immunosuppression precipitated six rejection episodes and were preventable, while the remaining 15 were true breakthrough crises. The overall rejection rate was 50%, with 92.3% of initial rejection episodes occurring within five weeks of steroid withdrawal. Rejection episodes were responsive to steroid therapy alone in 73.2% of cases. No graft loss from rejection has occurred after a mean follow-up interval of 8.5 months. At present, 33 patients (63.5%) are off steroids. In HLA-identical recipients, all but one successfully completed the protocol and 75% are currently steroid-free. In haplotype-matched patients, 87.5% completed the protocol and 60% are steroid-independent. Comparison with well-matched control groups on steroids failed to reveal any difference in graft or patient survival, rejection, infection, or mean serum creatinine level. No discriminating risk factors could be identified that were predictive of steroid withdrawal success or failure. In select patients, early steroid withdrawal can be accomplished without jeopardizing graft function. Long-term follow-up is required to assess the risk-benefit ratio of steroid withdrawal upon immunosuppressive morbidity.

Adult↗

Cadaveric renal transplantation in the cyclosporine and OKT3 eras.

With advances in clinical immunosuppression, results in organ transplantation continue to improve. During a 52-month period, 507 cadaver renal transplants were performed, including 435 primary and 72 nonprimary transplants. All patients were managed with quadruple immunosuppression (prednisone, azathioprine, sequential MALG and cyclosporine). Our experience is divided into pre-OKT3 (n = 228) and OKT3 (n = 279) eras. All kidneys were harvested locally and preserved with pulsatile machine perfusion. The mean duration of preservation was 30.1 hours, with an organ utilization rate of 98.1%. The preservation-related dialysis rate was 13.6%, and primary nonfunction occurred in 8 kidneys (1.6%). Actuarial patient survival in primary and secondary transplant recipients was 90% at 3 years. Overall primary graft survival was 81.6% and nonprimary graft survival, 61.1%. However, the current OKT3 era is characterized by improved patient survival (98% vs 90%, p = 0.001) and primary graft survival (91% vs 80%, p = 0.002) at 1 year when compared with the previous era. Forty-nine patients have received OKT3 therapy, with 31 grafts (63.3%) successfully rescued. Cadaveric renal transplantation with machine preservation, quadruple therapy, and OKT3 rescue is associated with excellent early graft function, reduced acute rejection, and improved patient and allograft survival, even in high-risk recipients.

Adolescent↗

Kidney retransplantation in the cyclosporine era.

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.

Blood Transfusion↗

Pancreas transplantation with pancreaticocystostomy and quadruple immunosuppression.

Forty-three whole-pancreas transplantations with pancreaticocystostomy were performed. Eighteen patients received pancreas transplants after previously receiving living-related kidney transplants, 18 patients received simultaneous kidney and pancreas transplants, and seven patients received pancreas transplants after previously receiving cadaver kidney transplants. All patients were immunosuppressed with quadruple immunosuppression including antilymphocyte globulin, prednisone, cyclosporine, and azathioprine. Overall graft survival for pancreas transplants is 73.1%. In the group with pancreas after living-related kidney, 1-year graft survival was 50% for the pancreas and 95.4% for the kidney. In the pancreas after cadaver kidney group, pancreas and kidney survival rates were 100% at 1 year, and in the simultaneous pancreas and kidney group, pancreas 1-year graft survival was 87.5% and kidney transplant survival was 93.8%. Overall patient survival at 1-year is 95.6%. Technical complications occurred in 21 patients. These included wound infections, intra-abdominal abscess formation, bleeding, and disruption of the pancreaticocystostomy. We believe that pancreas transplantation can now be performed with acceptable graft and patient survival.

Adult↗

Infectious complications in adults with bone marrow transplantation and T-cell depletion of donor marrow. Increased susceptibility to fungal infections.

The infectious complications of bone marrow transplantation were reviewed in 43 adults, 22 of whom received transplants from HLA-matched donors without T-cell depletion and 21 of whom received donor marrow pretreated with the murine anti-T-cell monoclonal antibody CT-2 and complement. Recipients of HLA-mismatched, T-cell-depleted transplants had a higher rate of bacteremia (1.33 compared with 0.64 per patient, p = 0.05) and especially systemic fungal infections (0.92 compared with 0.14 per patient, p less than 0.001) than recipients of transplants from HLA-identical donors without T-cell depletion; two thirds of these infections occurred during the granulocytopenic period early after transplantation. Recipients of HLA-identical but T-cell-depleted transplants also had significantly more systemic fungal infections (0.77 per patient, p less than 0.001). T-cell depletion was associated with delayed engraftment, more prolonged granulocytopenia, and more severe lymphopenia and was shown by stepwise multivariate regression analysis to be the most powerful predictor of systemic fungal infection (r = 0.512, p less than 0.0001). Whereas ex-vivo T-cell depletion may reduce the risk of severe graft-versus-host disease, it may predispose the patient to infection, especially with fungi.

Adult↗